Exploring the Relationship between Gut Microbiota and Breast Cancer Risk in European and East Asian Populations Using Mendelian Randomization

Background: Several studies have explored the potential link between gut microbiota and breast cancer; nevertheless, the causal relationship between gut microbiota and breast cancer remains unclear. This study investigated the causal relationship between gut microbiota and breast cancer in European and East Asian populations using a Mendelian Randomization (MR) analysis approach. Methods: We utilized summary statistics from genome-wide association studies (GWAS) of the gut microbiome from the MiBioGen project with summary data from GWAS on breast cancer from the FinnGen consortium and the IEU database. Preliminary statistical analyses were conducted using inverse variance weighting, supplemented by various sensitivity analysis methods, including MR-Egger regression, weighted median, weighted mode, simple median, and simple mode, to ensure the robustness of our findings. Heterogeneity and pleiotropy were assessed to avoid misleading conclusions caused by unconsidered confounders or non-specific effects of genetic variants, ensuring that the results reflect a genuine causal relationship. Results: In European populations, four types of gut microbiota were associated with breast cancer. The genus Erysipelatoclostridium was positively associated with the risk of breast cancer, with an odds ratio (OR) of 1.21 (95% confidence interval [CI] 1.083–1.358), false discovery rate (FDR) = 0.0039. The class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae, which belong to the same phylogenetic system, showed a consistent negative association with breast cancer risk, with an OR of 0.757 (95% CI 0.616–0.930), FDR = 0.0281. In East Asian populations, three types of gut microbiota were related to breast cancer. The Eubacterium ruminantium group was positively associated with breast cancer risk, with an OR of 1.259 (95% CI 1.056–1.499), FDR = 0.0497. The families Porphyromonadaceae and Ruminococcaceae were negatively associated with breast cancer risk, with ORs of 0.304 (95% CI 0.155–0.596), FDR = 0.0005, and 0.674 (95% CI 0.508–0.895), FDR = 0.03173, respectively. However, these two taxa had limited instrumental variables, restricting the statistical power and potentially affecting the interpretation of the results. Conclusion: A causal link between specific gut microbiota and breast cancer exists. This finding enhances our understanding of the relationship between the gut microbiome and breast cancer and offers potential directions for developing prevention and treatment methods.